Cardio-active oxido-bufadienolides

ABSTRACT

CARDIO-ACTIVE OXIDO-BUFADIENOLIDES OF THE FORMULA   3-(R-O-),4,5-(-O-),14-(HO-),17-(2-(O=)-2H-PYRAN-5-YL)   ANDROSTANE   WHEREIN R IS HYDROGEN OR LOWER ACYL, AND A METHOD FOR MAKING THEM.

"US. Cl. 260-23957 United States Patent 1 3,641,009 CARDIO-ACTIVE OXIDO-BUFADIENOLIDES Kurt Radscheit, -Kelkheim, Taunus, Ulrich Stache and Werner Haede, Hofheim, Taunus, Werner Fritsch, Neuenhaiu, Taunus, and Ernst Lindner, Frankfurt am Main, Germany, assignors to Farbwerke Hoechst Aktiengesellschaft vormals Meister Lucius & Bruning, Frankfurt am Main, Germany No Drawing. Filed Dec. 2, 1969, Ser. No. 881,582

Claims priority, application Germany, Dec. 5, 1968,

P 18 12 943.6 Int. Cl. C07c 173/04 2 Claims ABSTRACT OF THE DISCLOSURE Cardio-active oxido-bufadienolides of the formula wherein R is. hydrogen or lower acyl, and a method for making them.

-The present invention relates to oXido-bufadienolides of the general formula 1 ice Per-acid A) (III) The reaction is carried out in an inert solvent at room temperature. As per-acid, monoperphthalic acid, perbenzoic acid or mono-chloro-perbenzoic acid is preferably used. The reaction is completed after some hours.

For preparing the oxido-bufadienolides acylated in 3- position, the S-hydroxy compounds are esterified in the usual manner with lower aliphatic carboxylic acids. For this purpose, there are especially suitable acetic acid and halogenated acetic acids such as chloro-, bromoor iodoacetic acid. Propionic acid, too, may be used for the esterification. The acylation is advantageously effected by treatment with the corresponding carboxylic acid anhydride in the presence of pyridine at room temperature.

The products of the present invention are novel and they are distinguished by a strongly marked-cardioactivity. They are therefore suitable for the medicinal treatment of heart damages, especially in the case of cardiac insufiiciency or tachycardia. They are preferably administered orally in the form of tablets or drages which contain, in addition to the active substances, the usual. adjuvants and excipients, for example lactose, starch, tragacanth, etc. a

The products of the invention may aslo be used as intermediates in the manufacture of drugs, for example, by conversion of the 3-hydroxy compoundsinto corresponding substituted 3hydroxy derivatives such as ether or esters known in steroid chemistry. a

The following example illustrates the invention.

3 EXAMPLE 4,5 fl-oxido-Sfl, 14fi-dihydroxy-bufa-20(2 1 ,22(23 dienolide (mfifl-oxido-scillarenine A) 58 mg. of m-chloro-perbenzoic acid were added to a 5 solution of 80 mg. of scillarenine in 6.7 ml. of absolute methylene chloride and the whole was allowed to stand for 7 hours at room temperature. The reaction mixture was then poured into an excess of aqueous sodium bicarbonate solution and extracted several times with methylene chloride. The combined extracts were washed successively with sodium bicarbonate solution and water. After removal of the solvents by distilaltion, a solid residue remained behind which was dissolved in a large amount of hot methanol. The residue was removed by decanting and the solution was evaporated, taken up in a mixture of tetrahydrofurane and methanol and chromatographed on basic aluminum oxide of the activity degree II. Elution was effected consecutively with benzene, methylene chloride/methyl acetate mixtures and finally with ethyl acetate containings 5% of methanol. From the last eluate, there were obtained 40 mg. of the white crystalline epoxide which, after recrystallization from absolute ethanol, was found to melt at 236238 C. (Tottoli) Characteristic infrared bands: 3460, 3060, 1740 (shoulder), 1710, (measured in KBr) 1625-1630, 1530-1540, 1240 cm.- Ultraviolet spectrum: A ==297298 m e=6650.

We claim: *1. An oxido-bufadienolide of the formula 20 dienolide.

25 HENRY A. FRENCH, Primary Examiner Us. 01. X.R. 260999 

